Neuroscience and Neurobiology Commons^™

Role Of Proneurotrophin-P75ntr Signaling In A Mouse Model Of Depression, Kirsten Hodgson

All Graduate Theses and Dissertations, Fall 2023 to Present

Major depressive disorder, or depression, is among the leading causes of disability globally. Despite being a large public health challenge, depression remains difficult to treat as the underlying biology is still unknown and the currently available treatments are limited in effectiveness. This experiment was to test the efficacy of the drug LM11A-31, which works on the signaling pathway of proneurotrophin-p75NTR, a pathway that is not targeted by any currently used antidepressants. Male mice underwent a repeated forced swim, with all the mice receiving saline the first two days and then half the mice receiving saline and half receiving LM11A-31 before …

Covid‑19‑Related Risk, Resilience, And Mental Health Among Mexican American Mothers Across The First Year Of The Pandemic, Amy L. Non, Elizabeth S. Clausing, Sandraluz Lara‑Cinisomo, Kimberly L. D’Anna Hernandez

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Background Latina mothers have been especially affected by the pandemic and historically exhibit high rates of depression and anxiety. However, few longitudinal studies have assessed the effect of the pandemic on this vulnerable population. We hypothesized that COVID-19-related stressors would associate with psychological distress among Latina mothers across the first year of the pandemic.

Methods We investigated COVID-19-related impact, stigma, and fears across two critical time points and changes in these measures in relation to changes in maternal anxiety and depression among mothers of Mexican descent living in Southern California (n=152). Surveys were administered within 5–16 weeks of …

Affective Liking Influences Reward Processing In Depression: A Computational Eeg Approach, Garima Singh

Psychology ETDs

Reinforcement learning (RL) enables agents to learn through interaction with their environment. This empowers individuals to optimize actions in complex and dynamic settings. The component of event related potential (ERP) termed as the Reward Positivity (RewP) evidently signifies a fundamental reward prediction error (RPE) associated with rewards. This characteristic implies that it represents a fundamental computational process in the assessment of RL. When a reward is particularly pleasurable or liked by an individual, it tends to elicit an amplified RewP signal, reflecting the heightened positive affect. RPE arises from disparities between anticipated and actual rewarding outcomes and is known to …

The Eyes Beyond The Screen: Digital Media Policy And Child Health, Yahia Al-Qudah

Research Symposium

Background: Modern communication technology and digital media have provided society with a foundation for instant messaging. Pictures, videos, and texts connect individuals with families, friends, and the world. Consequently, digital media has accelerated exposure to risk in which children and adolescents are most vulnerable. This project’s objective is to 1) congregate and highlight current knowledge about the impact of digital media on child health, and 2) underline deficiencies in related laws and regulations as well as offer solutions in digital media policy.

Methods: A systematic literature review was conducted through the JAMA Pediatrics database with keywords such as “digital media,” …

Examining The Emergence Of Mood And Anxiety Molecular Phenotypes Resulting From Chronic Prenatal Nicotine Exposure In Cerebral Organoids, Emma K. Proud

Electronic Thesis and Dissertation Repository

Prenatal nicotine exposure (PNE) from maternal smoking disrupts regulatory processes vital to fetal development. These changes result in long-term behavioural impairments, including mood and anxiety disorders, that manifest later in life. However the relationship underlying PNE, and the underpinnings of mood/anxiety molecular phenotypes remains elusive. To model nicotine exposure during prenatal development, our study used human cerebral organoids that were chronically exposed to nicotine and collected for molecular analyses. Short-term, nicotine altered molecular markers of neural identity, mood/anxiety disorders and those involved in maintaining the excitatory/inhibitory (E/I) balance in the cortex. RNA sequencing further revealed transcriptomic changes in genes pertaining …

Identification Of Structural Brain Alterations In Adolescents With Depressive Symptomatology, J. Bashford‑Largo, R. James R. Blair, Karina S. Blair, Matthew Dobbertin, Ahria Dominguez, Melissa Hatch, Sahil Bajaj

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

Introduction: Depressive symptoms can emerge as early as childhood and may lead to adverse situations in adulthood. Studies have examined structural brain alternations in individuals with depressive symptoms, but findings remain inconclusive. Furthermore, previous studies have focused on adults or used a categorical approach to assess depression. The current study looks to identify grey matter volumes (GMV) that predict depressive symptomatology across a clinically concerning sample of adolescents.

Methods: Structural MRI data were collected from 338 clinically concerning adolescents (mean age = 15.30 SD=2.07; mean IQ = 101.01 SD=12.43; 132 F). Depression symptoms were indexed via the Mood …

Assessment Of The Triple Reuptake Inhibitor Diclofensine: Effort-Based Decision-Making In A Rodent Model Of Motivational Dysfunction, Sofia Papanikolaou

Holster Scholar Projects

Serotonin-selective reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications. Despite their popularity, they remain relatively ineffective at treating effort-related motivational symptoms of depression such as fatigue and anergia. Increasing research on triple reuptake inhibitors (TRIs) that target three neurotransmitters—dopamine, serotonin, and norepinephrine—has suggested that TRIs could have efficacy in targeting motivational dysfunction due to their dopaminergic effects. Previous research has shown that the dopamine depleting agent tetrabenazine can reliably induce motivational deficits in rats, as evidenced by a shift towards low-effort behavior in effort-based choice tasks, and provide a validated approach to creating a model of motivational dysfunction. …

Oral Contraceptives And Affective Disorders: Neurobiology And Informed Choice, Sophia Mae Drezner

Scripps Senior Theses

Pregnancy prevention and female reproductive freedom have been some of the most contested political issues for decades. Abortion, a fundamental part of women’s healthcare, divides liberals and conservatives on an international scale. The consequences of unintended pregnancy without safe and reliable contraception are widespread, disproportionately impacting women of color, trans and non-binary folks, and poorer communities. The birth control pill is the most common form of oral contraception (OC) globally. Many people with ovaries begin the pill or other hormonal contraceptive (HC) methods as young as 11 years old. Exogenous progesterone and estrogen are known to impact mood, affect, physiology, …

Effects Of Home-Based High-Intensity Interval Training Versus Continuous Walking On Cognition In Overweight And Obese Women, Kelsey C. Bourbeau

Health, Exercise, and Sports Sciences ETDs

Objective: The purpose of the present study was to determine whether six weeks of home-based high-intensity interval training versus six weeks of moderate-intensity walking improves cognition, depression, and anxiety in women that are overweight or obese. Design: A randomized control trial design. Subjects: Twelve sedentary women characterized as overweight or obese were randomized into either a six-week home-based high-intensity interval training (HIIT, n = 6, 26.6 ± 8.9 years, 37.4 ± 4.9% body fat) group or a six-week moderate-intensity walking (Walk, n = 6, 22.5 ± 3.7 years, 40.2 ± 4.1% body fat) group. Main Measures: Pre- and post-intervention, participants …

Psychophysiological Effects Of Increasing Awareness Of Nondual Consciousness In Young Adults With Depression And Anxiety, Milena Braticevic

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

Young adults increasingly suffer from anxiety and depression during the time of transition into adulthood. This research study examined the effects of increasing awareness of nondual consciousness in young adults who were experiencing various levels of anxiety and depression. The methodology was mixed-method and included four 1-hour group-based sessions over 4 weeks. Increasing awareness of nondual consciousness through educational, experiential, and behavioural components resulted in reduction in the average depression score from 19.4 (borderline clinical depression) to 10 (normal), and reduction in the average anxiety score from 12.7 (moderate anxiety) to 6.9 (mild). Participants reported increased mental, emotional, physical, and …

Role Of The Default-Mode Network During Narrative Integration In Major Depressive Disorder, Darren Ri-Sheng Liang

Electronic Thesis and Dissertation Repository

How brain activity is synchronized across individuals during narrative comprehension has previously been characterized by functional magnetic resonance imaging (fMRI) in healthy and patient populations. To our knowledge, there has been limited investigation as to how it is affected by major depressive disorder (MDD). We addressed this issue with fMRI through examination of inter-subject synchronization in the default mode network (DMN), brain structures which have previously been implicated in MDD pathology. Twenty-two patients with MDD and 20 matched control participants listened to Intact versus Scrambled versions of an auditory narrative; these experimental conditions differed in the degree of temporal integration …

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Regaining Effort-Based Food Motivation: The Drug Methylphenidate Reverses The Depressive Effects Of Tetrabenazine In Female Rats, Deanna Pietrorazio

Honors Scholar Theses

Tetrabenazine (TBZ), a vesicular monoamine transporter type 2 (VMAT-2) inhibitor, depletes dopamine and induces motivational deficits and other depressive symptoms in humans. Methylphenidate (MPH) is a dopamine transport blocker that is used to enhance motivational function. Previous studies have shown that in male rats, TBZ induces a shift in effort-related choice such that a low-effort bias is induced. In male rats this occurs at a dose range of 0.75-1.0 mg/kg TBZ, and this effect is reversible with co-administration of MPH. Recent studies have shown that females need a higher dose of TBZ (2.0 mg/kg) to show the low-effort bias. The …

The Various Nervous System Drugs Commonly Used For Treatment And The Disparities In Availability Of These Drugs In Minority Groups, Iman Haurami

Honors Scholars Collaborative Projects

The nervous system is a complex network in our body that is responsible for actions, reflexes, and even sensations. With the brain being part of the CNS, many common nervous system disorders are due to a defect in the central nervous system and the functions of this organ. These disorders include mental health problems, degenerative diseases, seizures, infections, and other possible genetic diseases. Many of these diseases are common in society and constantly researched. Even though these diseases are common, treatment accessibility and effects on people of minority groups are overlooked compared to the focus on majority groups. For drug …

An Abductive Argument From Depression And Anxiety To Christian Personal Holiness, Kelly Douglas Burchett

Masters Theses

The science on pathological depression and anxiety (D&A) describes religion and spirituality's (R/S) insulating and immunizing effects in roughly 72 to 85 percent of all relevant articles. But the descriptivism of science cannot assign any normative value to a theological worldview. Deductive logic favors theism via Leibnizian contingency, Kalām cosmology, objective morality, fine-tuning of the universe, and abstract conceptualism. The information in DNA, the irreducible complexity of intracellular machinery, the improbability of folded proteins, and the support for common modular design over common ancestry establish a design inference for all of life. Unguided naturalistic simulations fail to surmount the complexity …

Depression And Behavioral Changes Associated With Social Media Dependency During Covid-19 Pandemic Among University Students In Bangladesh: A Cross- Sectional Study, Sushmita Karmokar, Md. Ashraful Islam, Mohammad Hamid Al Muktadir, Rakibul Hasan, Abu Montakim Tareq, Mohammad Nurul Amin, Talha Bin Emran

Makara Journal of Health Research

Background: With its rapid spread, the coronavirus disease 2019 (COVID-19) pandemic had a detrimental effect on students’ psychological well-being, depression, and behavioral changes due to indefinite educational leaves, lockdowns, restricted outdoor activities, and excess use of social media. This study aims to assess the relationship of social media exposure with the psychological well-being, depression, and behavioral changes of Bangladeshi university students.

Methods: A web-based cross-sectional survey was carried out on 530 students from June 17 to July 10, 2020, to evaluate psychological well-being, depression, behavioral changes, and social media exposure via self-reported measures.

Results: The prevalence of …

The Disproportionate Impact Of Covid-19 On Women, Ava Stallone

Honors Scholar Theses

The impact of COVID-19 is placing a large strain on women. This can be seen through reports of mental health and financial concerns. Women are more vulnerable to COVID-19 related economic effects due to existing gender inequalities, which in turn may also have a negative effect on mental health. Through this study gender disproportion is looked at between mental health and COVID-19 financial concerns among women and men. The aim is to asses how COVID-19 financial concerns may be contributing to stress, anxiety, and depression. It is hypothesized that; women will report worse mental health and greater economic concerns than …

Behavioral, Physiological, And Molecular Characterization Of Long-Term Administration Of A Novel Estrogen Receptor Beta Agonist In A Mouse Model Of Menopause, Aaron William Fleischer

Theses and Dissertations

The menopausal loss of circulating hormones, including estrogens, is associated with negative symptoms, such as hot flashes, anxiety and depression, cognitive decline, and weight gain. Although estrogenic hormone therapies (HT) prevent many of the negative symptoms related to the menopausal transition, these same therapies are associated with increased health risks, such as the development of breast and ovarian cancers, which is mediated by the activation of the a (ERa), but not b (ERb), estrogen receptor isoform. Furthermore, ERb agonism has previously been shown to reduce preclinical indices of hot flashes, memory decline, anxiety, and depression. As most ERb agonists are …

The Development And Evaluation Of Novel Da Transport Inhibitors And Their Effects On Effort-Related Motivation: A Review, Mukund Desibhatla

Honors Scholar Theses

Depression is a debilitating disorder that can cause motivational deficits such as psychomotor retardation, anergia, apathy, and fatigue. Recent research indicates that these motivational deficits, and potential pathways of therapeutic intervention, can be studied in animal models involving rats and mice. Treatments with the VMAT-2 inhibitor tetrabenazine (TBZ) and cytokine interleukin-1ß (IL-1ß) can create a low-effort bias and impair effort-related motivation (Nunes et al. 2013, 2014). A number of high-affinity DA transport inhibitors such as d-amphetamine, methylphenidate, and cocaine can restore extracellular DA, albeit with the cost of undesirable effects such as high abuse liability. These observations have led researchers …

Implementation Of A Guideline For Major Depressive Disorder In A Private Practice Clinic, Doreen Phillips

Doctor of Nursing Practice

Major depressive disorder (MDD) is a chief mental health illness that carries a profound economic burden. Many who suffer from MDD find little to no relief with traditional pharmacological interventions.The 2010 American Psychiatric Association Guidelines for Treatment of Patients with MDD recognized TMS as a second-line treatment choice. Several double-blind, randomized controlled trials illustrated the efficacy and safety of TMS as a viable treatment option for MDD. The purpose of this project was to implement standardized processes through the use of a treatment guideline to help provide comprehensive treatment options for patients suffering from moderate to severe major depressive disorder …

The Effects Of The Atypical Dopamine Uptake Inhibitor Ce-158 On Extracellular Dopamine In The Nucleus Accumbens, Julia Neri

Honors Scholar Theses

Major Depressive Disorder (MDD) is characterized by symptoms such as cognitive dysfunctions, inflammatory changes, and motivational symptoms such as amotivation, fatigue, and anergia. While depressed people are commonly treated by traditional antidepressants such as serotonin reuptake inhibitors (SSRIs), previous studies have reported that SSRI medications do not treat fatigue and anergia symptoms well, and in some cases, can even worsen those symptoms. Subjects treated with dopamine (DA) uptake inhibitors, on the other hand, have been less likely to report symptoms of anergia and fatigue compared to those treated with SSRIs. Common DA uptake inhibitors such as methylphenidate and amphetamines, however, …

Influences Of Salvinorin A And Sex Differences On Depressive- And Anxiety-Like Behaviors In A Chronic Mild Stress Paradigm, Sarah Mitchell

Theses

Kappa opioid receptors are colocalized with dopamine receptors and are frequently associated with depression, anxiety, stress, and drug use and abuse. KOR antagonism has widely been considered anti-depressive and anxiolytic in animal models while agonism is pro-depressive and anxiogenic. However, recent findings suggest that SalvA, a natural kappa agonist derived from a plant in the mint family, can reduce depressive- and anxiety-like behavior in rats. The current study investigated the effects of chronic mild stress on behavior, attenuation by SalvA, and sex differences. 52 Long-Evans rats, 26 males and 26 females, were exposed to six weeks of CMS. Animals received …

The Role Of Diet In The Onset Of Depression: A Biochemical Connection Between Nutrition And Mental Health, Katlin Wildeman

Senior Honors Theses

Depression is a major clinical concern, having a complex onset and the presence of multiple, often unidentifiable causes. Depression affects millions of individuals worldwide, with a high prevalence in regions of the world with a Western-style diet as compared to regions with a Mediterranean diet. A Western-style diet consists of foods high in sugar, fat, and processed meats and grains, whereas the Mediterranean diet contains significantly more vegetables, fruits, lean meats, and whole grains. The link between diet and mental health disorders has implications for individuals of all ages who are hesitant to turn to medication. In addition to presenting …

New Approaches To Symptomatic Treatments For Alzheimer’S Disease, Jeffrey Cummings

School of Medicine Faculty Publications

Background: Successful development of agents that improve cognition and behavior in Alzheimer’s disease (AD) is critical to improving the lives of patients manifesting the symptoms of this progressive disorder. Discussion: There have been no recent approvals of cognitive enhancing agents for AD. There are currently 6 cognitive enhancers in Phase 2 trials and 4 in phase 3. They represent a variety of novel mechanisms. There has been progress in developing new treatments for neuropsychiatric symptoms in AD with advances in treatment of insomnia, psychosis, apathy, and agitation in AD. There are currently 4 AD-related psychotropic agents in Phase 2 trials …

Ketamine Pre-Exposure Does Not Influence Later-Life Responses To Reward-Related Stimuli In Female C57bl/6 Mice, Israel Garcia

Open Access Theses & Dissertations

Preclinical work indicates that exposure to traditional antidepressant medications, in adolescent and adult female subjects, alters reward-related behavior later in life. In recent years, the anesthetic ketamine (KET), now used as a fast-acting antidepressant, has shown promising therapeutic efficacy for the management of depression. However, the potential long-term behavioral consequences of KET exposure across development have not been thoroughly assessed. Thus, to address this issue, we examined if KET exposure, during adolescence or early adulthood, results in enduring alterations in responsivity to the rewarding properties of sucrose and cocaine later in life. Specifically, female C57BL/6 mice were randomly assigned to …

The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc

Electronic Thesis and Dissertation Repository

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess different …

The Influence Of Neural Reward Processing On Memory In Depression, Nathan M. Hager

Psychology Theses & Dissertations

Theories and research suggest that depression involves impaired reward sensitivity and a deficit in memory for rewarding stimuli. Some researchers propose that this memory deficit may result from reduced neural reward sensitivity, which impairs the encoding of reward-related memories, but few studies have directly probed this connection. Such research may benefit from examining the reward positivity (RewP), an event-related potential (ERP) previously linked to reduced reward sensitivity in depression. Undergraduates with high or low self-reported depression completed a task in which they chose one of three doors, revealing a neutral word written in a color which indicated an outcome of …

Investigating The Neurobiology Of Motivational Deficiencies In Major Depressive Disorder: 5-Ht1b Receptor Involvement In Behavioral Effects Of Fluoxetine (Prozac), Sarah Ferrigno

University Scholar Projects

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) are the most commonly prescribed treatments for depression. Although efficacious for symptoms such as a depressed mood, SSRIs do not alleviate symptoms of amotivation, anergia, and fatigue. Furthermore, in clinical and preclinical studies, SSRIs have been shown to exacerbate motivational impairments and general fatigue. It is likely that fluoxetine-induced dysfunctions are due to overstimulation of one or more 5-HT receptors, with one possible candidate being the 5-HT_1B receptor. Therefore, the aim of the study was to evaluate the role of 5-HT_1BRs in fluoxetine-induced amotivation using a rodent behavioral …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …